This invention relates to a medicament-coated minus power anterior chamber ocular implant for placement in a phakic eye to correct refractive errors such as myopia, a method of preparing such an implant and a method of using such an implant in a myopic phakic human eye.
It is well known to those skilled in the field of ophthalmology that there has previously been, and continues to be, a need for a successful anterior chamber ocular implant in the phakic eye to compensate for refractive errors such as high myopia or to create a specific refraction to assist in visual function. For example, U.S. Pat. No. 4,676,792 (Praeger) discloses the use of an uncoated anterior chamber minus power lens having a planar anterior-facing surface and a concave posterior-facing surface in the treatment of myopia. In addition, the recent use of uncoated implants as a surgical approach for patients having high myopia that is not satisfactorily corrected with spectacles or contact lenses has been attempted in France, as described in Colin et al., Refractive and Corneal Surgery, Vol. 6 (July/August 1990), pp. 245-51 and Baikoff et al., Refractive and Corneal Surgery, Vol. 6, (July/August 1990), pp. 252-60.
However, it has been acknowledged by those skilled in the art that there are significant risks involved in the use of such anterior chamber implants in the eye. For example, when such an implant is inserted into the eye, temporary or permanent adhesions of the implant to delicate intraocular structures may result, causing damage to these structures to ensue either immediately or over the long term. In addition, once the implant is in position, it may cause similar adhesions due to mechanical and/or chemical inflammation leading to fibrosis of a progressive nature and damaging of the intraocular tissue, thereby making subsequent removal of the implant a complex, dangerous surgical procedure. Other problems associated with such implants are cataract formation, secondary glaucoma, corneal edema, hyphema, and progressive endothelial cell loss, in addition to other complications.
As observed in Ophthalmology Alert, Vol. 1, No. 11 (November 1990), pp. 41-42, several American manufacturing companies which were preparing to begin clinical trials of anterior chamber ocular implants in the United States are now likely to abandon these studies, due to the attendant risks associated with the implants and the difficulty of obtaining approval of the federal Food and Drug Administration (FDA) for the use of the implants. In view of the foregoing, it would clearly be advantageous to employ a minus power anterior chamber ocular implant having a compatible medicament coating which would ameliorate and/or prevent the occurrence of the above-described problems associated with such implants.
It is also well known to those skilled in the art that an intraocular lens, when surgically inserted, is predominantly designed to replace a previously or simultaneously removed cataractous lens. However, although the implantation of intraocular lenses has constituted an appreciable surgical advance, such implantation has been known to cause immediate or late damage to the corneal endothelium, immediate or late inflammatory responses in the anterior and/or posterior segments of the eye, immediate or late secondary fibrosis and/or neovascularization, and other problems. In general, the phakic eye is more reactive than the aphakic eye, i.e. in the phakic eye, inflammatory reactions tend to be greater resulting in a concomitant increase in damage to the eye. Firstly, in the aphakic eye no lens pulls on the ciliary body; thus the ciliary body is in a "resting state" and tends to undergo some degree of atrophy. Therefore, an inflammatory response will be less in the aphakic eye. Secondly, the phakic eye has a shallower anterior chamber (i.e. the average antero-posterior depth is less) than the aphakic eye, and the iris has a greater surface area contacting the lens. Therefore, if an inflammatory reaction occurs in the phakic eye, there is a greater area of adherence of the iris to the anterior surface of the anatomic lens.
To overcome the above-described problems associated with the use of intraocular lenses to replace cataractous lenses, the use of intraocular lenses having various coatings has previously been disclosed. For example, U.S. Pat. No. 4,170,043 (Knight et al.) discloses coated intraocular lenses made of an acrylic resin having a coating to prevent adhesion of the intraocular lens to the corneal endothelium, the coating being polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl cellulose, hydroxypropyl methylcellulose, dextran, hydroxyethyl starch, methylcellulose or guar gum. However, some of these coatings have been found to cause inflammatory reactions and have proven to be unsatisfactory in clinical practice.
West German patent application No. 2,556,665 discloses coated intraocular lenses wherein the coating is a silicon rubber, such as methyl or methylphenyl siloxane. U.S. Pat. No. 4,240,163 (Galin) discloses coated intraocular lenses wherein the coating is a compatible medicament such as sulfated polysaccharide. Also, intraocular lenses having a covalent attachment of heparin to a polyamine that is ionically adsorbed onto an intraocular lens surface have been disclosed in product literature of Pharmacia AB of Uppsala, Sweden entitled "Surface Modified IOLs: A New Approach to Cataract Surgery," pp.17-19.
A further risk involved in the use of such anterior chamber implants in the eye is the potential for the implanted lens to touch the cornea and/or to contact the anatomic lens and/or the iris with resultant complications. However, the above-mentioned possibility of the lens touching adjacent anatomical structures may be avoided or mitigated by vaulting the lens in such a way as to minimize the chance of this occurrence.
In view of the foregoing, it will be apparent to those skilled in the art that some of the problems associated with the use of anterior chamber ocular implants employed to correct refractive errors in the phakic eye differ from those associated with the use of intraocular lenses employed as replacements for surgically removed cataractous lenses. For example, the use of implants in the phakic eye may actually cause cataract formation in the natural lens which remains in situ, whereas the use of intraocular lenses in patients having cataract removal cannot induce such an effect, as the natural lens has been replaced by the intraocular lens.
It is one object of this invention to provide a minus power anterior chamber ocular implant for placement in the anterior chamber of an eye having an anatomic lens in situ. The implant comprises a negative artificial refracting lens having at least one concave surface, a surface coating comprising a compatible sulfated polysaccharide medicament, and means for positioning the artificial lens in the anterior chamber of the eye to prevent contact between the implant and the anatomic lens. The implant may be surgically implanted in the phakic eye to compensate for refractive errors, which avoids the concomitant problems described above. The implant may subsequently be removed from the eye, if necessary.
It is one feature of this invention that the coating may be bonded covalently, by ionic attraction, or hydrogen bonding to the surface of the implant. It is another feature of this invention that the sulfated polysaccharide coating may be selected from the group consisting of heparin, heparin sulfate, chondroitin sulfate, dermatan sulfate, chitosan sulfate, xylan sulfate, dextran sulfate, and sulfated hyaluronic acid. It is yet another feature of this invention that the coating may be additionally complexed with compounds having anticoagulation properties, such as antithrombin. It is yet another feature of this invention that the coating may additionally comprise one or more compounds capable of absorbing ultraviolet and other short wavelength radiation.
It is one advantage of the coated implant of this invention that it avoids attraction and minimizes the adherence of white blood cells, pigment granules and intraocular tissue to its surface. It is another advantage of this invention that it avoids stimulation of white cell activity and enzyme release which results in corneal endothelial destruction and dysfunction. It is yet another feature of this invention that cataract formation secondary to surgical trauma and/or short and long term inflammation may be minimized and/or avoided. It is yet another advantage of this invention that flare, white cells, vitreous reaction, cystoid macular edema, hyopyon, uveitis, and secondary glaucoma typically associated by those skilled in the art with the use of anterior chamber eye implants may be avoided.
It is another object of this invention to provide a method of preparing the above-described minus power anterior chamber ocular implant, wherein the implant avoids the above-discussed problems when it is surgically implanted into the eye, and may subsequently be removed from the eye if necessary.
It is one feature of the method of preparing such an implant that the coating may be bonded covalently, by ionic attraction, or hydrogen bonding to the surface of the implant. It is another feature of this method that the sulfated polysaccharide coating may be a selected from the group consisting of heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, chitosan sulfate, xylan sulfate, dextran sulfate, and sulfated hyaluronic acid. It is yet another feature of this method that the coating may be additionally complexed with compounds having anticoagulation properties, such as antithrombin. It is yet another feature of this method that the coating may additionally comprise one or more compounds capable of absorbing ultraviolet and other short wavelength radiation. It is yet another feature of this method that plasma-treating may first be used to treat an uncoated implant, and the medicament may thereafter be bonded to the plasma-treated surface.
It is one advantage of this method that it avoids attraction and minimizes the adherence of white blood cells, pigment granules and intraocular tissue to its surface. It is another advantage of this method that it avoids stimulation of white cell activity and enzyme release which results in corneal endothelial destruction and dysfunction. It is yet another feature of this method that cataract formation secondary to surgical trauma and/or short and long term inflammation may be minimized and/or avoided. It is yet another advantage of this method that flare, white cells, vitreous reaction, cystoid macular edema, hyopyon, uveitis, and secondary glaucoma typically associated by those skilled in the art with the use of anterior chamber eye implants may be avoided.
It is yet another object of this invention to provide a method of using the coated anterior chamber ocular implant of this invention in the treatment of myopia, wherein the implant is surgically implanted in the phakic eye to compensate for refractive errors, thereby advantageously avoiding the above-described problems. The implant may subsequently be removed from the eye, if necessary.